The automated testing of blood samples has become an important part of many medical investigations. Automated instruments' speed and ease of use has made them the preferred method of producing a complete blood count (CBC) in hospital laboratories, despite the errors and inaccuracies induced by the method. The errors usually do not cause much problem in routine testing, but there has recently been a growing concern in the literature about incorrect cell sizing due to the automated methods.
The specification describes novel mechanical methods of minimizing the errors produced by existing technology and describes ways to improve the accuracy and resolution of current technology, in particular when used with red blood cells or whole blood samples.
Automated particle counters typically use a sensor which detects particles in a restricted flow, producing a measure of particle size and count for each particular type of particle. The sensor usually detects a change in an electrical field, an alteration in the light scatter from a laser, a change in the magnetic field density or magnetic flux, or changes in the optical, acoustic or other physical properties of the cells or cell suspension and/or suspending liquid. Whatever type of sensor is used, it produces a signal which is a product of a particle's size, shape, trajectory, number and other properties, some of which may be measured concomitantly. Electronic particle counters which use a direct or alternating current as a method to detect particles can be referred to as electronic particle sizing devices (hereinafter referred to as EPS), and produce a characteristic change in voltage or current, usually recorded as a voltage pulse as a particle passes through a restriction (aperture).
Electronic particle sizing relies on two electrodes suspended in a conducting solution which are isolated from each other except for a single conducting channel which is traversed by cells or other small particles in suspension. As a particle passes through the channel (aperture) measurable physical characteristics of the channel temporarily change in proportion to the particle's size. By measuring the properties of these changes, the size and concentration of particles is determined. This is performed on red cells, white cells and platelets and any free cell suspension and may be combined with stains or other techniques to further differentiate the cells by any means (i.e. optically, NMR etc).
In an ideal system, the size of a particle passing through the sensor would be described exactly by the amplified signal. However, due to theoretical limits and practical limitations of the current technology, the signal degrades before it arrives at the input to the amplifier. Noise in the system is induced by procedural errors (incomplete mixing, ignoring the sample pH, ignoring particle shape, etc) and from the physical design of the instrument (noise pick-up from long cables, impedance from the cables, poor electrode design etc) and inherent noise sources described by physical laws such as Johnson noise (white noise).
With the existing electrode design of EPS apparatus, the electrical field created by the electrodes passes extensively into the fluid body. As cells approach or exit the aperture they distort the electrical field which disturbs the charge density inside and around the aperture and degrades the electrical signal.
In existing apparatus, both sides of an electrode are exposed to electro magnetic interference (EMI). The pick up of EMI by the electrodes acting as antennae can lead to noise in the signal thereby reducing the system's sensitivity. Furthermore, since the electrodes are suspended in the liquid they are spaced at some distance from the aperture. This requires the surface area of the electrodes to be relatively large, which again increases the EMI pick up and makes the electrodes expensive in terms of materials. Further noise in the circuit is created by mechanical pick up from physical movement of the electrodes, which is inherent and cannot be prevented since the electrodes are freely suspended in the liquid.
With the existing electrode design, the electrical connections from the amplifier to the electrodes tend to be relatively long and this creates additional noise from the long signal paths. It is well known that the distance between the electrodes and the amplifier is particularly significant in increasing noise at this critical point in the circuit.
Generally, part of the leads connected to the electrode are submersed or at least exposed to the liquid, requiring them to be made of the same, expensive noble metal as the electrode itself.
A further problem with the existing apparatus is that it is laborious to clean the electrodes and the aperture. Each component must be removed from the apparatus independently to be cleaned. In practice this is often not done because it is too onerous. EP-A-0,246,011 describes a particle counter in which the electrodes are integrally formed on a sapphire wafer in which an aperture is located. A silicon layer is formed vitaxially on one side of the sapphire wafer and integrated circuits formed on a silicon layer using conventional photolithographic techniques. The aperture is formed by drilling a hole in the sapphire wafer. The piece of sapphire required for this is prohibitively expensive.
The present invention seeks to solve the above mentioned problems and confers additional benefits by providing an electrode assembly which has excellent performance, is easy to remove and replace and service and is simple to incorporate with other electronic devices into the apparatus.